Kiss János, Balla Bernadett, Kósa P János, Borsy Adrienn, Podani János, Takács István, Lazáry Aron, Nagy Zsolt, Bácsi Krisztián, Szlávy Eszter, Szendrôi Miklós, Speer Gábor, Orosz László, Lakatos Péter
Semmelweis Egyetem, Altalános Orvostudományi Kar Ortopédiai Klinika Budapest Karolina út 27. 1113.
Orv Hetil. 2010 Oct 3;151(40):1656-65. doi: 10.1556/OH.2010.28967.
Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS1 gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in fibro-osseous lesions. The aim of the investigation was to identify genes that are differently expressed in fibrous vs. non-fibrous human bone and to describe the relationships between these genes using multivariate data analysis.
Six bone tissue samples from fibrous dysplastic female patients and 7 bone tissue samples from non-fibrous dysplastic women were examined. The 6 female fibrous samples were taken from the fibrous dysplastic lesion itself while the control samples of 7 non-fibrous dysplastic females were taken from the femoral neck during the hip replacement procedure. The expression differences of selected 118 genes were analyzed in TaqMan probe based quantitative real-time RT-PCR system.
The Mann-Whitney U test indicated significant differences in the expression of 27 genes of fibrous dysplasial and non fibrous dysplasial individuals (p≤0.05). Nine genes were significantly up-regulated in fibrous dysplasial women compared to non fibrous dysplasial ones and eighteen genes showed a down-regulated pattern. These significantly altered genes coding for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro-inflammatory cytokines and lipid metabolism-affected substrates. Canonical variety analysis demonstrated that fibrous dysplastic and non fibrous dysplastic bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via a G-protein coupled pathway and BMP cascade as well as genes coding for extracellular matrix composing molecules.
The significantly altered gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.
骨纤维发育不良是一种孤立的骨骼疾病，由GNAS1基因的体细胞激活突变引起，在纤维性骨病变中出现异常的未矿化基质过度产生和大量未分化骨细胞积聚。本研究的目的是鉴定在纤维性与非纤维性人类骨骼中差异表达的基因，并使用多变量数据分析描述这些基因之间的关系。
检查了6例骨纤维发育不良女性患者的骨组织样本和7例非骨纤维发育不良女性的骨组织样本。6例女性纤维性样本取自骨纤维发育不良病变本身，而7例非骨纤维发育不良女性的对照样本取自髋关节置换手术期间的股骨颈。在基于TaqMan探针的定量实时RT-PCR系统中分析了所选118个基因的表达差异。
Mann-Whitney U检验表明，骨纤维发育不良和非骨纤维发育不良个体的27个基因表达存在显著差异（p≤0.05）。与非骨纤维发育不良女性相比，9个基因在骨纤维发育不良女性中显著上调，18个基因呈下调模式。这些显著改变的基因编码小胶原蛋白分子、细胞外基质消化酶、转录因子、粘附分子、生长因子、促炎细胞因子和受脂质代谢影响的底物。典型变量分析表明，骨纤维发育不良和非骨纤维发育不良的骨组织可以通过对通过G蛋白偶联途径和BMP级联控制的众多基因以及编码细胞外基质组成分子的基因进行多重表达谱分析来区分。
在骨纤维发育不良的人类骨组织中观察到的显著改变的基因表达谱可能为骨纤维变性的发病机制提供进一步的见解。
